The following discussion of the background of the invention and references cited therein are not admitted to be prior art to the invention.
Cellular signal transduction is a fundamental mechanism whereby external stimuli that regulate diverse cellular processes are relayed to the interior of cells. One of the key biochemical mechanisms of signal transduction involves the reversible phosphorylation of tyrosine residues on proteins. The phosphorylation state of a protein is modified through the reciprocal actions of tyrosine phosphatases (TPs) and tyrosine kinases (TKs), including receptor tyrosine kinases and non-receptor tyrosine kinases.
A tyrosine protein kinase named PYK2, is described in U.S. patent application Ser. No. 08/460,626, filed Jun. 2, 1995, which is a continuation-in-part application of U.S. patent application Ser. No. 08/357,642, filed Dec. 15, 1994, both of which are hereby incorporated herein by reference in their entirety including any drawings. PYK2 contains an N-terminal domain, a catalytic domain, two proline-rich regions, potential Src homology 2 (SH2) binding regions, and a region homologous to the focal adhesion targeting domain.
A type of protein found in Drosophila, called Drosophila retinal degeneration B protein(rdgB)is described in Vihtelic et al., J. of Cell Biology 122, :1013-1022, 1993. The sequence described in this reference, however, contained a false stop codon sequencing error and thus the authors were not aware that the Drosophila rdgB contains a PYK-2 binding domain. In addition, this sequence was incorrectly identified as a member of the 6-transmembrane domain family of proteins. These rdgB proteins function in many sensory and neuronal cells of the fly and are directly associated with sight in the fly.
The sequence of a genomic clone of a portion of C. elegans has been placed on a computer database, and (although unappreciated), this sequence contains an rdgB sequence with introns. Thus, the GENEBANK database contains raw data of the nucleotide sequence of a series of genomic clones of c. Elegans. Using portions of the human rdgb sequence, the present invention identifies an open reading frame that has been to this point unrecognized. An rdgB was thus found segregated into 14 exons in two separate cosmids C54C6 (assc. #Z77131) and MO1F1 (assc. #Z46381).